Search results for "DISCOVERY"

showing 10 items of 4119 documents

Safety and side effects of human and ovine corticotropin-releasing hormone administration in man.

1991

Synthetic human and ovine corticotropin-releasing hormone (hCRH, oCRH) are commonly used as a diagnostic tool of the hypothalamo-pituitary-adrenal axis. In this paper reports about side effects after various modes of CRH-application are analyzed and compared to our corresponding data of human studies with hCRH and oCRH. Generally, CRH is well tolerated after single administration and interval-application of standard doses, although minor side effects appear sometimes after higher doses (greater than 200 micrograms hCRH, oCRH) of CRH-bolus-injections. Predominantly the cardiovascular system (e.g. tachycardia, hypotension, flushing) is affected; neuropsychological symptoms are only seen spora…

TachycardiaSingle administrationmedicine.medical_specialtyContinuous infusionCorticotropin-Releasing HormoneDizzinessCorticotropin-releasing hormoneBiological ClocksRisk FactorsInternal medicineTachycardiaDrug DiscoverymedicineFlushingAnimalsHumansIn patientDrug InteractionsGenetics (clinical)SheepHuman studiesDose-Response Relationship Drugbusiness.industryRespirationHead injuryGeneral Medicinemedicine.diseaseHormonesEndocrinologyAnesthesiaMolecular Medicinemedicine.symptombusinessHormoneKlinische Wochenschrift
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The "Neurocentric" Approach to Essential Hypertension: How Reliable is the Paradigm of Hyperkinetic Hypertension? A Focus on the Sympathetic Nervous …

2017

BACKGROUND: Clinic resting heart rate (RHR), is one of the cardiovascular parameters more easily measurable. In the general population RHR has been associated with total and cardiovascular mortality and higher rate of vascular events. OBJECTIVE: The case of essential hypertension is in some ways peculiar: in the past decades has often been attributed to hypertensive subjects higher values of RHR than healthy controls as a result of the effects of the different factors leading to the development of essential hypertension itself, first of all the presence of an increased tone of the sympathetic nervous system Methods: Several excellent articles debated the issue of autonomic dysfunction in es…

Tachycardiaresting heart ratemedicine.medical_specialtySympathetic nervous systemRestPopulation030204 cardiovascular system & hematologyEssential hypertension03 medical and health sciences0302 clinical medicinehyperkinetic hypertensionHeart RateInternal medicineDrug DiscoveryHeart ratemedicineAnimalsHumans030212 general & internal medicineeducationPharmacologyeducation.field_of_studysympatho-vagal balancebusiness.industryessential hypertensionmedicine.diseaseBlood pressuremedicine.anatomical_structurePathophysiology of hypertensionAmbulatorySympathetic nervous systemCardiologymedicine.symptombusiness
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β-Amino alcohols from anilines and ethylene glycol through heterogeneous Borrowing Hydrogen reaction

2017

Abstract Borrowing Hydrogen (BH), also called Hydrogen Autotransfer (HA), reaction with neat ethylene glycol represents a key step in the preparation of β-amino alcohols. However, due to the stability of ethylene glycol, mono-activation has rarely been achieved. Herein, a combination of Pd/C and ZnO is reported as heterogeneous catalyst for this BH/HA reaction. This system results in an extremely air and moisture stable, and economic catalyst able to mono-functionalize ethylene glycol in water, without further activation of the diol. In this work, different diols and aromatic amines have been explored affording a new approach towards amino alcohols. This study reveals how the combination of…

TandemHydrogen010405 organic chemistryChemistryOrganic ChemistryDiolBorrowing hydrogenchemistry.chemical_element010402 general chemistryHeterogeneous catalysis01 natural sciencesBiochemistry0104 chemical sciencesCatalysischemistry.chemical_compoundPhase (matter)Drug DiscoveryOrganic chemistryEthylene glycolTetrahedron
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Syntheses of dopaminergic 1-cyclohexylmethyl-7,8-dioxygenated tetrahydroisoquinolines by selective heterogeneous tandem hydrogenation

2002

Abstract We describe the preparation in a ‘one-pot’ sequence 1-cyclohexylmethyl 7,8-dioxygenated tetrahydroisoquinoline, substituted and unsubstituted in the C ring by application of the Photo–Fries transposition, followed by a tandem reduction–cyclization and further reduction. Indeed, we have accomplished for the first time regioselective hydrogenation of the benzylic ring of the tetrahydroisoquinoline systems. All 1-cyclohexylmethyl THIQ synthesized were able to displace D2 dopamine receptor from its specific binding site in rat striatal membranes, while the N-methylated derivatives showed also affinity for D1 dopamine receptors.

TandemTetrahydroisoquinolineStereochemistryOrganic ChemistryDopaminergicRegioselectivityRing (chemistry)Biochemistrychemistry.chemical_compoundchemistryDopamine receptorTHIQDrug DiscoverymedicineBinding sitemedicine.drugTetrahedron
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Experimental Studies on the Influence of Surfactants on Intestinal Absorption of Drugs Cefadroxil as model drug and sodium taurocholate as natural mo…

2011

The influence of the natural bile acid surfactant sodium taurocholate (CAS 81-24-3) on colic and duodenal (i.e. the proximal third of the small intestine) absorption of cefadroxil (CAS 50370-12-2) was studied using the in situ rat gut technique, and compared with the effect of sodium lauryl sulfate (CAS 151-21-3), the most widely used synthetic anionic surfactant. Previously, the stability, compatibility, and micelle-solubilization characteristics of taurocholate were assessed in order to correct, when necessary, the absorption results. White the passive absorption rate constants (kf, h-1) determined in colon in the presence of increasing lauryl sulfate concentrations showed an asymptotic v…

Taurocholic AcidColonDuodenumSodiumBiological Availabilitychemistry.chemical_elementModels BiologicalMicelleIntestinal absorptionSurface-Active AgentsPulmonary surfactantDrug DiscoverymedicineAnimalsMicellesAntibacterial agentChromatographyChemistryCefadroxilHydrogen-Ion ConcentrationSmall intestineCephalosporinsRatsBioavailabilityPerfusionmedicine.anatomical_structureIntestinal AbsorptionCefadroxilAlgorithmsChromatography Liquidmedicine.drugArzneimittelforschung
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Synthesis of Fluorinated and Nonfluorinated Tebufenpyrad Analogues for the Study of Anti-angiogenesis MOA

2014

In this contribution we report the synthesis of fluorinated and nonfluorinated tebufenpyrad analogues to explore potential druglike properties through the phenotypic screening as part of the Lilly Open Innovation Drug Discovery (OIDD) program.

Tebufenpyradchemistry.chemical_compoundChemistryAnti angiogenesisStereochemistryDrug discoveryPhenotypic screeningOrganic ChemistryPhysical and Theoretical ChemistryCombinatorial chemistry
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Optimization of Polyphenols' Recovery from Purple Corn Cobs Assisted by Infrared Technology and Use of Extracted Anthocyanins as a Natural Colorant i…

2022

An ecofriendly extraction technology using infrared (IR) irradiation Ired-Irrad® was applied to purple corn cobs to enhance polyphenol recovery for the first time. The IR extraction efficiency was compared to that of the water bath (WB) method. Response surface methodology (RSM) using a central composite design was conducted to determine the effect of the experimental conditions (extraction time and treatment temperature) and their interactions on the total polyphenol and anthocyanin yields. Optimal extraction of total phenolic compounds (37 mg GAE/g DM) and total monomeric anthocyanins (14 mg C3G/g DM) were obtained at 63 °C for 77 min using IR as an extraction technique and water as a sol…

TechnologyPlant ExtractsOrganic ChemistryBrassica napusPharmaceutical SciencePolyphenolsWaterZea maysAnalytical ChemistryAnthocyaninsBlat de moroChemistry (miscellaneous)Drug DiscoveryMolecular MedicineColorants en els alimentsTecnologia dels alimentsPhysical and Theoretical Chemistrypurple corn cobs; infrared-assisted extraction; response surface methodology; anthocyanins; natural colorant
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Synthetic studies on the preparation of oxygenated spongiane diterpenes from carvone

2003

Abstract The paper describes a new diastereoselective approach to oxygenated spongiane diterpenes functionally related to natural dorisenones. The strategy followed for the preparation of the spongiane framework, a B→AB→ABC→ABCD approach, is based on the preparation of epoxydecalone 11 (AB rings) from R-(−)-carvone, followed by an intramolecular Diels–Alder reaction for the construction of the C ring (compound 26 ). Further manipulation of the Diels–Alder adduct functionality allows the completion of the spongiane framework and the elaboration of several oxygenated spongiane-type compounds. The structures of two compounds 27 and 31 , has been established by single-crystal X-ray crystallogra…

TerpeneCarvonechemistry.chemical_compoundchemistryStereochemistryIntramolecular forceOrganic ChemistryDrug DiscoveryOrganic chemistryBiochemistryDiels–Alder reactionAdductTetrahedron
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New route to herbertanes via a Suzuki cross-coupling reaction: synthesis of herbertenediol

2001

Abstract The synthesis of herbertenediol, a relevant member of the herbertane-type sesquiterpene family, is described. The synthesis is based on a new general approach to this group of sesquiterpenes where the herbertane skeleton is constructed using a Suzuki cross-coupling reaction and a [2,3]-sigmatropic Still–Wittig rearrangement as key synthetic steps.

Terpenechemistry.chemical_compoundchemistryGroup (periodic table)StereochemistryOrganic ChemistryDrug DiscoverySesquiterpeneBiochemistryHerbertenediolCombinatorial chemistryCoupling reactionTetrahedron
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Ultrasound assisted reductive cleavage of eudesmane and guaiane γ-enonelactones. Synthesis of 1α,7α,10αH-guaian-4,11-dien-3-one and hydrocolorenone f…

2001

Abstract Ultrasound enhances the rate of reductive cleavage of the C6–oxygen bond of sesquiterpene enonelactones. trans-Eudesmanolides 1c–1g, cis-eudesmanolides 2a–2c, and trans-guaianolides 4a–4d react with Zn in acetic acid–H2O under sonochemical conditions to afford the corresponding sesquiterpene acids 3a–3g and 5a–5d, respectively in good yields. Starting from 5d two natural guaianes 1α,7α,10αH-guaian-4,11-dien-3-one (6) and hydrocolorenone (7) have been prepared in good yields through a straightforward sequence.

Terpenechemistry.chemical_compoundchemistryReductive cleavageOrganic ChemistryDrug DiscoveryUltrasound assistedSesquiterpeneBiochemistryMedicinal chemistrySantoninSonochemistryTetrahedron
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